childhood trauma, which permanently alters the stress response to acute stressors into adulthood (Nemeroff, 2004). Further, dysregulation of the extra hypothalamic CRF system is associated with the development and maintenance of alcoholism in both preclinical (Koob, 2008, Koob, 2010) and clinical (Sinha, 2001) models. Specifically, neurobiological models have emphasized the role of CRF in extrahypothalamic systems in the extended amygdala including dysregulated response to stressors, which is thought to contribute to the maintenance of alcoholism (Heilig & Koob, 2007, Koob, 2010). To that end, pharmacotherapies that can effectively target CRF system dysregulation are of great interest for the treatment of alcohol dependence (AD) (Ciccocioppo et al., 2009). For example, a selective CRHR1 antagonist was found to reduce alcohol self-administration in animals with a history of chronic alcohol exposure (Funk et al., 2007) and to block stress-induced reinstatement in alcohol preferring rats (Hansson et al., 2006).
